This is a Phase 1/2a, nonrandomized, open-label, parallel assignment, single-dose, dose-escalation, and dose-expansion study to evaluate the safety and clinical activity of PBCAR269A, with or without nirogacestat, in adults with r/r MM. Study subjects in Cohort A will receive PBCAR269A and study subjects in Cohort B will receive PBCAR269A and nirogacestat. At each dose level, study subjects in Cohort A and Cohort B will receive the same dose of PBCAR269A. In Cohort B, all study subjects will follow the same dosing regimen of nirogacestat. This study was terminated prior to beginning of Phase II due to lack of sufficient therapeutic effect
This is a multicenter, nonrandomized, open-label, parallel assignment, single-dose, dose-escalation, and dose-expansion study to evaluate the safety and clinical activity of PBCAR269A, with or without nirogacestat, in adults with r/r MM. Before initiating the study treatment PBCAR269A, all study participants will be administered lymphodepletion chemotherapy. The initial lymphodepletion chemotherapy regimen will be composed of fludarabine and cyclophosphamide during the Screening Period. Study subjects in Cohort B will also receive nirogacestat. On Day 0 of the Treatment Period, study participants will receive a single intravenous (IV) infusion of PBCAR269A. All subjects are monitored during the treatment period through Day 28. All subjects who receive a dose of PBCAR269A, with or without nirogacestat, will be followed in a separate long-term follow-up (LTFU) study for 15 years after exiting this study.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
48
Allogeneic anti-BCMA CAR T-cell
Fludarabine is used for lymphodepletion.
Cyclophosphamide is used for lymphodepletion.
Allogeneic anti-BCMA CAR T-cell
City of Hope
Duarte, California, United States
University of California San Francisco
San Francisco, California, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Columbia University Irving Medical Center
New York, New York, United States
MD Anderson
Houston, Texas, United States
Maximum Tolerated Dose (MTD) of PBCAR269A
To determine the maximum tolerated dose (MTD), which is defined as the dose level at which fewer than 33% of patients experience a dose limiting toxicity (DLT) using a 3+3 strategy.
Time frame: Day 1 - Day 28
Number of Participants with Dose Limiting Toxicity(ies)
To assess adverse events as dose limiting toxicities as defined by the protocol and CTCAE v5.0.
Time frame: 1 year
Objective Response Rate of Patients
To assess ORR to treatment with PBCAR269A through Day 360 will be noted using the IMWG response criteria. The ORR is defined as the proportion of study participants meeting the definition of response within the study population to the response evaluable population. ORR will be summarized by number and percentage of study participants meeting the definition of ORR along with the corresponding exact 95% CIs. DoR, defined as the duration (days) from initial response to disease relapse, progression, or death will be descriptively analyzed using Kaplan-Meier methods. The number of study participants achieving DoR at 3, 6, 9, and 12 months will also be calculated. Exploratory efficacy analyses include changes from Baseline in CBC counts, CAR T cells, cytokines, and CRP levels.
Time frame: 1 year
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